CCCTC-Binding Factor Mediates the Transcription of Insulin-Like Growth Factor Binding Protein 5 Through EZH2 in Ulcerative Colitis.

Dan Gu, Ting Cao, Shijie Yi, Ya Liu, Chao Fan

Digestive diseases and sciences 2023 Mar

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Ulcerative colitis (UC) features chronic, non-infectious inflammation of the colon. Insulin-like growth factor binding protein 5 (IGFBP5) has been indicated to be related to various inflammation-related diseases. However, its association with UC remains largely unclear. Here, we investigate the role of IGFBP5 in colonic mucosal epithelial cell injury in UC. Differentially expressed genes in the colonic tissues of UC mice were screened using the Gene Expression Omnibus database, and IGFBP5 was identified. UC mice were developed using dextran sulfate sodium, and IGFBP5 expression in the colonic tissues of UC mice was confirmed by immunohistochemistry and RT-qPCR. The effects of IGFBP5 in vivo and in vitro were investigated by intraperitoneal injection of adeno-associated virus into UC mice or by transfection with an IGFBP5 overexpression plasmid into lipopolysaccharide-treated colonic mucosal epithelial cells. The mechanisms causing IGFBP5 deletion in UC were predicted by bioinformatics analysis and ChIP-qPCR and verified by rescue experiments. IGFBP5 was reduced in UC. IGFBP5 impaired the NFκB pathway in the colonic tissue of UC mice and ameliorated inflammatory infiltration and colonic mucosal cell injury. IGFBP5 depletion was associated with H3K27me3 modification, which was induced by EZH2. CTCF was responsible for recruiting EZH2 to the promoter region of IGFBP5. CTCF inhibition repressed UC progression by reducing H3K27me3 modification via the discouragement of the enrichment of EZH2 in the IGFBP5 promoter. CTCF modulates H3K27me3 modification of the IGFBP5 promoter by recruiting EZH2, thereby downregulating IGFBP5 to accentuate colonic mucosal epithelial cell injury in UC mice. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Dan Gu, Ting Cao, Shijie Yi, Ya Liu, Chao Fan. CCCTC-Binding Factor Mediates the Transcription of Insulin-Like Growth Factor Binding Protein 5 Through EZH2 in Ulcerative Colitis. Digestive diseases and sciences. 2023 Mar;68(3):778-790